Department of Neurosurgery, Shandong Provincial Hospital, Shandong University, No. 9677 Jingshi Road, Jinan, 250014, Shandong, People's Republic of China.
Hum Cell. 2019 Oct;32(4):548-556. doi: 10.1007/s13577-019-00279-9. Epub 2019 Sep 5.
Glioblastoma is a common malignant primary intracranial tumor characterized by rapid invasive growth and a high recurrence rate after surgery. MicroRNAs (miRNAs) are involved in cell proliferation, differentiation, and apoptosis, and abnormal miRNA expression is associated with the occurrence and progression of various tumors, including glioblastomas. The aim of this study was to determine the levels of miR-148a and integrin subunit alpha 9 (ITGA9) in glioblastoma tissues and cells and their involvement in cancer cell proliferation and migration. Glioblastoma tissues from 19 patients and two glioblastoma cell lines (U87 and LN229) were used in this study. The effects of miR-148a on cell viability, proliferation, colony formation, migration, and invasion were assessed. Glioblastomas were xenografted in nude mice to examine the effects of miR-148a overexpression on tumor growth in vivo. Levels of ITGA9 mRNA and protein in glioblastoma tissues were detected by quantitative reverse transcription PCR and western blot analysis, respectively. The interaction between miR-148a and ITGA9 was determined by a dual-luciferase reporter gene assay. We found that the overexpression of miR-148a decreases the proliferation, clustering, migration, and invasiveness of U87 and LN229 cells and inhibits the tumorigenicity of xenografted glioblastomas. We confirmed that ITGA9 is the target of miR-148a. Restoration of ITGA9 expression reversed the decreased viability, migration, and invasiveness of glioblastoma cells induced by miR-148a overexpression. Our findings indicate that miR-148a can suppress the malignant phenotype of glioblastoma by targeting ITGA9 and identify ITGA9 as a potential therapeutic target for glioblastoma.
胶质母细胞瘤是一种常见的恶性原发性颅内肿瘤，其特征为快速侵袭性生长和手术后高复发率。微小 RNA（miRNA）参与细胞增殖、分化和凋亡，异常的 miRNA 表达与多种肿瘤的发生和进展有关，包括胶质母细胞瘤。本研究旨在确定胶质母细胞瘤组织和细胞中 miR-148a 和整合素亚基α9（ITGA9）的水平及其在癌细胞增殖和迁移中的作用。本研究使用了 19 名患者的胶质母细胞瘤组织和两种胶质母细胞瘤细胞系（U87 和 LN229）。评估了 miR-148a 对细胞活力、增殖、集落形成、迁移和侵袭的影响。将 miR-148a 过表达的胶质母细胞瘤异种移植到裸鼠中，以体内观察 miR-148a 过表达对肿瘤生长的影响。通过定量逆转录 PCR 和 Western blot 分析分别检测胶质母细胞瘤组织中 ITGA9 mRNA 和蛋白的水平。通过双荧光素酶报告基因检测确定 miR-148a 和 ITGA9 之间的相互作用。我们发现 miR-148a 的过表达可降低 U87 和 LN229 细胞的增殖、集落形成、迁移和侵袭能力，并抑制异种移植胶质母细胞瘤的致瘤性。我们证实 ITGA9 是 miR-148a 的靶基因。恢复 ITGA9 的表达可逆转 miR-148a 过表达引起的胶质母细胞瘤细胞活力、迁移和侵袭能力的降低。我们的研究结果表明，miR-148a 通过靶向 ITGA9 抑制胶质母细胞瘤的恶性表型，并确定 ITGA9 是胶质母细胞瘤的潜在治疗靶点。
